Several reports exist on attempts to produce medicinally useful, biologically active substances by means of human macrophages. However, at the present time, the only promising route of harvesting such a biologically active substance in a practically useful quantity is by way of a cell line established from a tumor-bearing patient. Examples of human tumor macrophage cell lines established from a tumor-bearing patient include U-937 (International Journal of Cancer, 17, 565-577 (1976)), THP-1 (International Journal of Cancer, 26, 171-176 (1980)), J-111 (Blood, 10, 1010 (1955)), HL-60 (Nature, 270, 347 (1977)), KG-1 (Science, 200, 1153 (1978)) and K-562 (Blood, 45, 321-334 (1975)).
Referring to reports on attempts to obtain biologically active substances from these cell lines, the methods proposed by S. B. Mizel et al, Interleukins, Lymphokines, and Cytokines, Academic Press, Inc. 401-407 (1983) and T. Krakauer et al, Cellular Immunology, 80, 223-229 (1983) may be mentioned for the production of interleukin-1 from THP-1; R. Palacios et al, European Journal of Immunology, 12, 895-899 (1982) may be mentioned for the production of interleukin-1 from U-937; and R. H. Butler et al, Cellular Immunology, 78, 368-374 (1983) may be mentioned for the production of interleukin-1 from CM-S. E. V. Gaffney et al, Cancer Research, 43, 3668-3673 (1983), for instance, describes a method using THP-1 for the production of tumoricidal factors.
Human macrophage cell lines established from tumor-bearing patients may be stimulated by lipopolysaccharide, plant lectin or lymphocyte secretions to induce the secretion of a variety of biologically active substances as described in Proc. Natl. Acad. Sci. USA, 79, 5379-5383 (1982). However, since the output of such substances is very small and the kinds of cell lines are virtually limited to those mentioned above, the techniques are of little practical use.
Several methods for enabling human macrophages to proliferate may be contemplated, such as the method in which cells are tumorized with a virus or chemical carcinogen, the method which comprises picking up the desired cells from among serially passaged cells, and the method utilizing fusion with tumor cells, for instance. Of these and other methods, the cell fusion technique is the most suitable in that, once established, the technique is applicable to a large variety of cells and the problem of carcionogenic chemical residues can be obviated.
As regards past studies on the fusion of macrophages, it has been reported, for example, in A. H. Warfel, Experimental and Molecular Pathology, 28, 163-176 (1978) and S. Sone et al, Americal Journal of Pathology, 103, No. 2, 234-246 (1981), that giant cells are formed by fusion of homologous cells of some aminals such as mice, rats and rabbits. Regarding fusion between heterologous cells, the only report available describes that fusion between rat and mouse macrophages (P. Stahl et al, The Journal of Cell Biology, 93, 49-56 (1982)) and no report is known on a successful fusion between human macrophages.